Seeing how diabetes affects the nerves of patients in 3D

It is well known that diabetes causes nerve damage that can often lead to pain and numbness in the arms and the legs of patients. The condition of carpal tunnel syndrome affects healthy patients but it is more predominant in people affected by diabetes type I or II. Professor Lars Dahlin, hand surgeon at Skåne University Hospital and Lund University, operates on patients with this condition on a daily basis. During a visit to the ESRF as research infrastructure coordinator in Lund University, he discovered the potential the ESRF could offer in his research.

Until then, patient biopsies of peripheral nerves were evaluated using light or electron microscopy, which offer mostly 2D information. On ESRF’s ID16A beamline, however, the team led by Dahlin and Martin Bech, both from Lund University, managed to get new insights on how nerves change in diabetic patients. “This is a whole new way of studying nerves compared with histology, where you look at the tissue section by section in two dimensions. Here we get an image that allows us to rotate the nerve fiber and perceive details in a completely different way”, explains Martin Bech, medical radiation physicist at Lund University and one of the researchers behind the study.

The team imaged nerve samples extracted from the wrist of patients with diabetes type I, diabetes type II, and healthy patients during surgery and with consent. It is known that diabetes type I affects more severely the morphology of peripheral nervous system than diabetes type II, while the non-diabetic patients have normal nerve micro-architecture. Healthy nerves at wrist (so called posterior interosseous nerve) have around 6000 fibres per square millimeter, whilst nerves of type I diabetes patients have roughly 1000 fibres less.

The resulting data from the experiment was very rich and complex, so Dahlin and Bech collaborated with the Department of Applied Mathematics and Computer Science at the Technical University of Denmark (DTU) to analyze it.

The results showed that there are clusters of abnormally small fibres with an intertwined organization in sick patients. “Even nerve fibres regenerating in diabetic people show a disorganized structure as opposed to parallel arrangement of the fibres in healthy tissue”, explains Dahlin. “Another surprising result is that nerve fibres sprout from old ones in a specific pattern”, he adds.

“Thanks to X-ray holographic nanotomography, we could explore for the first time the 3D detailed structure of the nerve fibres and we now understand more about how the nerves react in diabetic patients and why these patients are more likely to get carpal tunnel syndrome”, Dahlin says. “We are still at the level of fundamental science, but we hope to analyze more specimens and quantify changes in larger samples in the near future”, he concludes.

“ID16A is increasingly becoming a reference in nanotomography of biological tissue. We will build up on the technical knowledge that we’ve acquired thanks to this experiment to push further the capabilities for applications in neurosciences and neuromedicine.”, explains Alexandra Pacureanu, scientist at the ESRF and co-author of the study.

Reference:

Dahlin, L.B., et al Sci Rep 10, 7592 (2020). https://doi.org/10.1038/s41598-020-64430-5.

Text and video by Montserrat Capellas Espuny.

Top image: An illustration showing the condition of carpal tunnel syndrome. Credits: www.scientificanimations.com